WO2022080022A1 - 生体粒子分取装置及び情報処理装置 - Google Patents

生体粒子分取装置及び情報処理装置 Download PDF

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Publication number
WO2022080022A1
WO2022080022A1 PCT/JP2021/031734 JP2021031734W WO2022080022A1 WO 2022080022 A1 WO2022080022 A1 WO 2022080022A1 JP 2021031734 W JP2021031734 W JP 2021031734W WO 2022080022 A1 WO2022080022 A1 WO 2022080022A1
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Prior art keywords
data
display
button
bioparticle
display area
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PCT/JP2021/031734
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English (en)
French (fr)
Japanese (ja)
Inventor
竜 鋤柄
康一朗 佐藤
宗哲 大沢
伸一 吉田
侑大 柳下
マルクオレル ブルン
肇 松田
Original Assignee
ソニーグループ株式会社
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Application filed by ソニーグループ株式会社 filed Critical ソニーグループ株式会社
Priority to DE112021005380.9T priority Critical patent/DE112021005380T5/de
Priority to JP2022557249A priority patent/JPWO2022080022A1/ja
Priority to US18/030,305 priority patent/US20230383235A1/en
Publication of WO2022080022A1 publication Critical patent/WO2022080022A1/ja

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/48—Automatic or computerized control
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/14—Optical investigation techniques, e.g. flow cytometry
    • G01N15/1425—Optical investigation techniques, e.g. flow cytometry using an analyser being characterised by its control arrangement
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M47/00—Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass
    • C12M47/04—Cell isolation or sorting
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00584—Control arrangements for automatic analysers
    • G01N35/00722—Communications; Identification
    • G01N35/00871—Communications between instruments or with remote terminals
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/14—Optical investigation techniques, e.g. flow cytometry
    • G01N15/1425—Optical investigation techniques, e.g. flow cytometry using an analyser being characterised by its control arrangement
    • G01N15/1427—Optical investigation techniques, e.g. flow cytometry using an analyser being characterised by its control arrangement with the synchronisation of components, a time gate for operation of components, or suppression of particle coincidences
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/14—Optical investigation techniques, e.g. flow cytometry
    • G01N15/1468—Optical investigation techniques, e.g. flow cytometry with spatial resolution of the texture or inner structure of the particle
    • G01N15/147—Optical investigation techniques, e.g. flow cytometry with spatial resolution of the texture or inner structure of the particle the analysis being performed on a sample stream
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N2015/1006—Investigating individual particles for cytology
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00584—Control arrangements for automatic analysers
    • G01N35/00722—Communications; Identification
    • G01N2035/00891—Displaying information to the operator
    • G01N2035/0091—GUI [graphical user interfaces]

Definitions

  • This disclosure relates to a biological particle sorting device and an information processing device. More specifically, the present disclosure relates to a bioparticle sorting device and an information processing device that display a screen relating to control and / or execution of a bioparticle sorting process.
  • a large number of graphs and / or a table of statistics are displayed on the screen of the information processing apparatus, for example, gate setting or adjustment is performed. Further, a desired biological particle is also separated by using the result of the analysis.
  • the device that performs the sorting is also called a cell sorter. Further, in recent years, a device for separating biological particles in a closed space has been proposed, and the device is also called a closed sorter.
  • Patent Document 1 includes a determination unit that determines whether to separate the fine particles based on the light generated by irradiating the fine particles flowing in the flow path.
  • a primary preparative determination is made to determine whether the microparticles belong to any of two or more different microparticle populations based on the characteristics of the light, and any of the microparticle populations in the primary preparative determination.
  • Disclosed is a fine particle sorting device that makes a secondary sorting determination to determine whether to sort the fine particles determined to belong to the above two or more different fine particle populations based on the specified particle composition ratio. ing.
  • the sorting process conditions such as the gate setting are set.
  • the setting is made via various data displayed on the screen as described above.
  • highly specialized knowledge for example, knowledge about biological particles and knowledge about sorting devices
  • Devices such as flow cytometers and cell sorters that have been commercially available so far are designed on the assumption that the user has such specialized knowledge.
  • a bioparticle sorting device such as a closed sorter
  • the user U wears work clothes and gloves for the clean room and bioparticle content.
  • the glove is a lab glove made of a material such as latex.
  • fine operations are often difficult.
  • a touch panel it is difficult to perform fine operations with the gloves on. Therefore, it is desirable to provide a user interface that is easy to use or operate even in such a state.
  • the main purpose of this disclosure is to improve the operability of the bioparticle sorting device that accepts input of various data by touch operation.
  • This disclosure is It is equipped with a touch-input display unit that displays a screen for setting processing conditions that accepts input of operation control data related to the preparative processing of biological particle-containing samples.
  • the processing condition setting screen has a first display area for displaying an operation flow for setting a preparative processing condition for a biological particle-containing sample, and a second display area for displaying measurement data related to the biological particle-containing sample. Including, The first display area is arranged at the end of the processing condition setting screen.
  • a bioparticle sorting device is provided.
  • this disclosure is It is equipped with a touch-input display unit that displays a screen for setting processing conditions that accepts input of operation control data related to the preparative processing of biological particle-containing samples.
  • the processing condition setting screen has a first display area for displaying an operation flow for setting a preparative processing condition for a biological particle-containing sample, and a second display area for displaying measurement data related to the biological particle-containing sample. Including, The first display area is arranged at the end of the processing condition setting screen. Information processing equipment is also provided.
  • FIG. 1 It is a schematic diagram which shows the example of the situation which operates the bioparticle sorting apparatus. It is a figure which shows the structural example of the biological sample analyzer of this disclosure. This is an example of a block diagram of the biological particle sorting device of the present disclosure. This is an example of a flow chart of processing performed by the biological particle sorting apparatus of the present disclosure. It is a figure which shows the example of the mode selection screen. It is a figure which shows the example of the identification information input screen. It is a figure which shows the example of the screen for setting a processing condition. It is a figure which shows the example of the screen for setting a processing condition. It is a figure which shows the example of the 1st display area. It is a figure which shows the example of the 2nd display area.
  • the first embodiment of the present disclosure (biological particle sorting device) (1) Device configuration example (2) Processing example (2-1) Display mode selection (2-2) First display mode (2-2-1) Screen configuration example displayed in the first display mode (2-1) 2-2-2) Example of processing in the first display mode (2-3) Second display mode (2-3-1) Configuration example of the screen displayed in the second display mode (2-3-2) No. (2) Example of processing in display mode (3) Modification example 3.
  • the second embodiment of the present disclosure (biological particle sorting system)
  • the preparative processing condition setting for the preparative processing by the bioparticle sorting device is performed via various data displayed on the screen, and the preparative processing condition is set. Often requires highly specialized knowledge. Therefore, it is considered difficult for the user such as the worker or the operator described above to properly use the conventional user interface. Therefore, it is desirable to provide a user interface that is easy for the user to use or operate.
  • the present disclosure provides a bioparticle sorting device including a display unit capable of touch input, which displays a screen for setting processing conditions that accepts input of operation control data related to the sorting processing of a bioparticle-containing sample.
  • the processing condition setting screen has a first display area for displaying an operation flow for setting a preparative processing condition for the biological particle-containing sample and a second display area for displaying measurement data regarding the biological particle-containing sample. And may be included. Further, the first display area may be arranged at the end of the processing condition setting screen.
  • the biological particle sorting device that displays the processing condition setting screen on the display unit is suitable for operation by touch input. The device is also easy to use, for example, for a user wearing gloves.
  • a researcher or a developer inputs operation control data using the first display mode, and a worker or an operator performs processing in the second mode.
  • the sorting process by the bioparticle sorting device can be executed via the operation screen. Therefore, different user interfaces can be presented to the researcher or developer and the worker or operator, and for example, a work environment suitable for each use can be provided.
  • the researcher or the developer transfers the operation control data (for example, work procedure information) related to the preparative processing operation to be performed by the worker or the operator via the processing condition setting screen. input.
  • the operation execution operation screen generated based on the operation control data is presented to the operator. This allows the researcher or developer to easily create instructions for the operator such as correct work procedures and / or precautions for each preparative process. Then, the operator can execute an appropriate preparative process according to the instruction displayed on the process execution operation screen, according to the designated work procedure, and referring to the precautions.
  • a user who operates the bioparticle sorting device in the first display mode is also referred to as a "first user", and a user who operates the bioparticle sorting device in the second display mode is referred to as a "second user”.
  • the first user may be a user who designs and / or develops a preparative process to be executed in the second display mode.
  • the first user is, for example, the above-mentioned researcher or developer.
  • the second user may be a user who operates the bioparticle sorting device according to the instruction input in the first display mode to execute the sorting process.
  • the second user is, for example, the operator or worker described above.
  • FIG. 2A shows a configuration example of the biological sample analyzer of the present disclosure.
  • the biological sample analyzer 6100 shown in FIG. 2A has a light irradiation unit 6101 that irradiates the biological sample S flowing through the flow path C with light, and a detection unit 6102 that detects the light generated by irradiating the biological sample S with light. , And an information processing unit 6103 that processes information about the light detected by the detection unit.
  • Examples of the biological sample analyzer 6100 include a flow cytometer and an imaging cytometer.
  • the biological sample analyzer 6100 may include a sorting unit 6104 that sorts specific biological particles P in the biological sample. As an example of the biological sample analyzer 6100 including the preparative unit, a cell sorter can be mentioned.
  • the detection unit 6102 may include an image pickup device such as a CCD or CMOS.
  • the detection unit 6102 can acquire an image of biological particles (for example, a bright-field image, a dark-field image, a fluorescent image, etc.) by the image pickup device.
  • the detection unit 6102 may include a signal processing unit that converts an electric signal obtained by a photodetector into a digital signal.
  • the signal processing unit may include an A / D converter as a device for performing the conversion.
  • the digital signal obtained by the conversion by the signal processing unit can be transmitted to the information processing unit 6103.
  • the digital signal can be handled by the information processing unit 6103 as data related to light (hereinafter, also referred to as "optical data").
  • the optical data may be optical data including, for example, fluorescence data. More specifically, the optical data may be light intensity data, and the light intensity may be light intensity data of light including fluorescence (may include feature quantities such as Area, Hight, Width, etc.). good.
  • the information processing unit 6103 includes, for example, a processing unit that executes processing of various data (for example, optical data) and a storage unit that stores various data.
  • the processing unit acquires the light data corresponding to the fluorescent dye from the detection unit 6102, the processing unit can perform fluorescence leakage correction (compensation processing) on the light intensity data.
  • the processing unit executes a fluorescence separation process on the optical data and acquires the light intensity data corresponding to the fluorescent dye.
  • the fluorescence separation treatment may be performed according to, for example, the unmixing method described in Japanese Patent Application Laid-Open No. 2011-232259.
  • the information processing unit 6103 may be configured to be able to output various data (for example, optical data or images). For example, the information processing unit 6103 can output various data (for example, a two-dimensional plot, a spectrum plot, etc.) generated based on the optical data. Further, the information processing unit 6103 may be configured to accept input of various data, for example, accepting a gating process on a plot by a user.
  • the information processing unit 6103 may include the output or an output unit (for example, a display) or an input unit (for example, a keyboard) for executing the input.
  • the sorting unit 6104 executes sorting of biological particles according to the determination result by the information processing unit 6103.
  • the preparative method may be a method in which droplets containing biological particles are generated by vibration, a charge is applied to the droplets to be sorted, and the traveling direction of the droplets is controlled by an electrode.
  • the method of sorting may be a method of controlling the traveling direction of the biological particles in the flow path structure to perform sorting.
  • the flow path structure is provided with, for example, a pressure (injection or suction) or charge control mechanism.
  • a chip having a flow path structure in which the flow path C branches to a recovery flow path and a waste liquid flow path downstream thereof, and specific biological particles are recovered to the recovery flow path. (For example, the chip described in JP-A-2020-76736) can be mentioned.
  • a bioparticle sorting device may have a touch input capable display unit D, for example, as shown in FIG.
  • the display unit may be arranged on any surface of the housing of the device, particularly on the side surface, for example, a user standing (or sitting) in the vicinity of the device.
  • the screen of the display unit may be arranged at a position where the touch input can be performed.
  • the processing condition setting screen or the processing execution operation screen described later may be displayed on the display unit.
  • the bioparticle sorting device according to the present disclosure may have an introduction unit I for introducing a bioparticle-containing sample into the device.
  • the touch operation may be a tap (single tap), a long tap, a double tap, or the like, but is not limited thereto.
  • the touch operation may be, for example, dragging, swiping, pinching in, or pinching out.
  • the type of touch operation may be appropriately selected by those skilled in the art.
  • FIG. 2B is an example of a block diagram of a bioparticle sorting device.
  • the bioparticle sorting device 100 according to the present disclosure includes a display unit 101 and an information processing unit 102.
  • FIG. 3 is an example of a flow chart of processing performed by the bioparticle sorting device.
  • the information processing unit 102 causes the display unit 101 to display the screen in accordance with the present disclosure.
  • the information processing unit 102 is configured to output data for displaying the screen.
  • the information processing unit 102 may be the information processing unit 6103 described in (1) above, but may be a separately prepared information processing unit.
  • the biological particle sorting device 100 may include a light irradiation unit 6101, a detection unit 6102, and a sorting unit 6104 described in (1) above, in addition to the display unit 101 and the information processing unit 102.
  • the information processing unit 102 causes the display unit 101 to output a mode selection screen prompting the user to select a mode.
  • the mode selection screen includes, for example, as shown in FIG. 4, a button for selecting a first display mode (First display mode button) and a button for selecting a second display mode (Second display mode button). ..
  • the mode selection screen may further include a button (Next button) for displaying the next processing screen after the mode is selected.
  • a more specific mode name may be displayed on each button displayed on the mode selection screen.
  • the first display mode may be displayed as a preparative processing condition setting mode, or may be displayed as a setting mode, a process development mode, a PD mode, or the like.
  • the second display mode may be displayed as a process execution operation mode, or may be displayed as an operation mode, an operation mode, an OP mode, or the like.
  • a button for selecting an administrator mode may be further displayed on the mode selection screen.
  • the information processing unit 102 can, for example, set or change the user's authority information.
  • the information processing unit 102 causes the display unit 101 to output a screen prompting the user to input the identification information.
  • the identification information may include a user ID (or user name), and may further include a password.
  • the screen has a user ID input field and a password input field, for example, as shown in FIG. The user enters the identification information in these fields.
  • the information processing unit 102 refers to the input identification information, and determines whether or not the operation of the apparatus in the selected mode is permitted for the identification information. If permitted, the information processing unit 102 advances the process to step S13. If it is not permitted, the information processing unit 102 displays, for example, a screen indicating that it is not permitted on the display unit 101, and returns the process to steps S11 or S12.
  • step S13 the process in the selected mode is executed.
  • the processing in each mode will be described in (2-2) and (2-3) below.
  • steps S12 and S13 may be omitted.
  • the fact that any mode is selected in step S11 may be used as identification information.
  • only step S12 may be executed without executing step S11. That is, the information processing unit 102 may display a screen for accepting input of identification information on the display unit 101, and shift to the first display mode or the second display mode according to the input identification information.
  • the bioparticle sorting device 100 (particularly, the information processing unit 102) accepts the input of operation control data related to the bioparticle sorting process.
  • the display unit 101 may be capable of touch input.
  • the display unit 101 displays a processing condition setting screen that accepts input of operation control data related to the preparative processing of the biological particle-containing sample.
  • the operation control data may be data used for executing the preparative process in the second display mode, and particularly includes data for generating a process execution operation screen in the second display mode.
  • FIG. 6 shows a configuration example of the processing condition setting screen displayed on the display unit 101 by the bioparticle sorting device 100 (particularly, the information processing unit 102).
  • the processing condition setting screen 200 shown in the figure is a setting operation flow display area (hereinafter also referred to as “first display area”) for displaying an operation flow for setting processing conditions for preparative processing. ) 201 and a measurement data display area (hereinafter, also referred to as “second display area”) 251 for displaying measurement data regarding a biological particle-containing sample.
  • first display area for displaying an operation flow for setting processing conditions for preparative processing.
  • second display area a measurement data display area for displaying measurement data regarding a biological particle-containing sample.
  • the first display area is arranged on the left side of the processing condition setting screen, and the second display area is arranged on the right side of the processing condition setting screen. May be done. Alternatively, even if the first display area is arranged on the right side of the processing condition setting screen and the second display area is arranged on the left side of the processing condition setting screen. good.
  • the first display mode it is often required to set detailed preparative conditions, which requires confirmation of detailed measurement data, or a large number of plot data may be displayed on one screen. You will need it.
  • it is also required to present the progress of the work or the operation to be performed next to the first user. Therefore, as described above, by arranging the two areas on the left and right, a large second display area can be secured, which makes it easier for the first user to check the measurement data, and by displaying the operation flow. , The first user can check the work status.
  • the arrangement of the first display area and the second display area may be changeable.
  • the former area is arranged on the right side and the latter area is arranged on the left side
  • the former area is arranged on the left side and the latter area is arranged on the right side.
  • the screen can be changed to a state.
  • the screen can be changed so as to be the opposite.
  • the first display area is arranged on the left side of the processing condition setting screen and the second display area is arranged on the right side of the processing condition setting screen.
  • the first display area may be arranged so as to be in contact with the right end of the processing condition setting screen, and the procedure button area may be arranged on the right side of the first display area, and in particular, the area may be arranged on the right end of the processing condition setting screen. May be done.
  • the color or shape of the button indicating the process being worked on may be different from the color or shape of the other buttons.
  • the processing buttons 204a indicating the process being performed may be shown in gray
  • the processing buttons 204b to 204e indicating other steps may be shown in white. This makes it easier to identify the process being worked on.
  • the second display area may be configured to display one or more plots and may include a plurality of plot data, for example as shown in the figure.
  • a plurality of plot data may be arranged in a grid pattern.
  • the display format of the plurality of plot data may be changed to a list (for example, arranged from top to bottom). It is possible to set a gate for each plot data. That is, the second display area may be configured to receive input of gate information for specifying bioparticles to be separated in the process by a touch operation.
  • the second display area may display one or more operation buttons, and may display one or more operation buttons for displaying data associated with the one or more plots.
  • the associated data is, for example, fluorescence correction matrix data.
  • the matrix display button 206 is shown in the figure.
  • the matrix display button (Matrix button) is a button for displaying a window for displaying and / or adjusting the fluorescence correction matrix used for generating the plot data displayed in the measurement data area.
  • the associated data may be, for example, back data used to generate the plot.
  • the back data may include, for example, statistical information of each gate.
  • the gate tree display button 207 is shown in the figure.
  • an inactive tab is a tab associated with a worksheet other than the active worksheet.
  • a worksheet associated with an inactive tab is also called an inactive worksheet.
  • the inactive worksheet may be, for example, a worksheet for preparative processing performed in the past and / or a worksheet for reference.
  • Inactive tabs may be grouped and displayed at the edge of the tab area 209 (eg, the right edge or the left edge).
  • the display position of the active tab in the tab area is fixed.
  • the tab area may be displayed so that the tab selected by the first user exists at the left end (or right end) in the tab area. In this case, the inactive tabs are placed at the right end (or left end).
  • the information processing unit 102 may display, for example, one active tab and one or two other tabs in the tab area, along with at least a portion of the worksheet name.
  • One or more tabs other than these may be configured to be displayed by pull-down, for example, to be displayed in a pull-down menu displayed by touching or selecting a predetermined button. This allows you to intuitively understand which worksheet is active (especially the worksheet being measured). In addition, even when many worksheets are open in a narrow screen, the worksheet names to be compared or referred to can be easily confirmed, and the worksheets can be switched by one touch or click. For example, pull-down buttons as indicated by reference numeral 213 in FIGS. 10A and 10B may be displayed in the tab area.
  • a pull-down menu may be displayed, for example, as shown in FIG. 10C.
  • the pull-down button is arranged in the active tab in FIGS. 10A and 10B, but may be arranged in the inactive tab, or may be arranged at another position in the tab area. May be good.
  • the information processing unit 102 may display a pull-down button for displaying a list of non-displayed worksheets by pull-down in the tab area.
  • the information processing unit 102 has a button for creating a new experiment file and a button for opening an existing experiment file in the setting information display area, as shown in the figure.
  • the displayed file open area 214 (Open / New Experiment area) and the property area 215 (Experiment properties area) for displaying the properties of the experiment file are displayed.
  • an export button for exporting open operation control data (indicated as an Export button in the figure) and / or the operation control data is saved.
  • a save button (shown as a Save button in the figure) may be displayed.
  • the information processing unit 102 causes the setting information display area to display the screen as shown in FIG.
  • the screen is a screen for controlling a process of acquiring data (optical data, particularly scattered light data and / or fluorescence data) related to biological particles in a biological particle-containing sample.
  • the information processing unit 102 causes the setting information display area to display the flow control area 216 (Flow control area) and the recording control area 217 (Record control area), as shown in the figure.
  • a button group for controlling the recording of the preparative determination result based on the set gate and data indicating the status of the recording are displayed.
  • the button group includes a start button (Record button) for starting the recording (or restarting the paused recording), a pause button (Pause button) for pausing the recording, and a pause button.
  • a start button for starting the recording (or restarting the paused recording)
  • a pause button for pausing the recording
  • a pause button for pausing the recording
  • an end button (Stop button) to end the recording.
  • the elapsed time of the recording operation, the number of events to be analyzed, and the like may be displayed.
  • the information processing unit 102 causes the setting information display area to display the screen as shown in FIG.
  • the screen is a screen for setting a gate for separating target bioparticles based on the optical data acquired in the data acquisition step.
  • the bioparticle sorting device 100 displays the flow control area 219 and the fluorescence correction setting area 220 (displayed as the Compensation control area in the figure) in the setting information display area.
  • a check box for selecting whether to apply the fluorescence correction (displayed as Apply compensation in the figure) and a loaded correction matrix are displayed.
  • a correction factor input box of 1 or more for adjusting the included correction factor (a numerical value 10.0 is input in the figure) is displayed.
  • the correction matrix is adjusted by inputting a numerical value to the correction alphanumerical input box.
  • the name of the applied correction matrix (displayed as default matrix for 4 laser in the figure), the button for loading the correction matrix (Load button), and the loaded correction matrix.
  • a button (Save button) for saving the adjusted correction matrix may be displayed.
  • the first user inputs settings (correction coefficient, etc.) related to the correction matrix in this area.
  • the input setting data regarding the correction matrix may be included in the operation control data, and in particular, a part of the "(a) processing condition data adopted by the processing apparatus that executes the processing in the second mode". May be included as.
  • the gate information setting may be appropriately executed by the first user. For example, generate plot data from the acquired optical data, set a gate on the generated plot data, expand the gate to generate more plot data, and set more gates on the plot data. do. By appropriately repeating the operations of plot data generation, gate setting, and expansion in this way, gate information for sorting the target biological particles is generated.
  • the generated plot data may be a two-dimensional plot or a one-dimensional plot, and the type of plot data may be appropriately selected by the first user. Further, the scattered light / fluorescence channel adopted as the axis of each plot data and the scale of the axis may be appropriately selected by the first user.
  • the information processing apparatus 102 selects such as displaying a cross-shaped indicator 223 for emphasizing the selected correction coefficient.
  • Image processing may be performed to emphasize the corrected correction coefficient. This makes it easier for the first user to confirm the correction coefficient selected by himself / herself.
  • the information processing unit 102 may be configured to accept adjustments of each correction coefficient in the correction matrix. The status of the adjustment is shown in FIG. 15B. As shown in the figure, the information processing apparatus 102 causes the slider 224 to be displayed in the vicinity of the selected position by the finger of the first user selecting the correction coefficient to be adjusted. Along with this, the information processing apparatus 102 may perform image processing for emphasizing the slider, such as coloring the window 221 in gray as shown in the figure. As shown in the figure, the slider may be an indicator that can be moved in the vertical direction, or may be an indicator that can be moved in the left-right direction or any other two directions. The information processing unit 102 may display the slider movement button 225 for moving the slider in the vicinity of the slider. The slider may be moved in response to the button being selected.
  • the information processing unit 102 may enlarge the box 226 displaying the selected correction coefficient and display it in the vicinity of the slider. As a result, the first user can easily confirm the value of the correction coefficient selected by himself / herself.
  • the information processing apparatus 102 changes the value of the correction coefficient in the box in response to the movement of the slider or the touch of the button.
  • the first user may adjust the correction matrix by operating the window.
  • the information processing apparatus 102 saves the corrected matrix data after the adjustment.
  • the corrected matrix data may be included in the operation control data, and in particular, as a part of the "(a) processing condition data adopted by the processing apparatus that executes the processing in the second mode". May be included.
  • the display or non-display of the window may be switched by touching the matrix display button, that is, the matrix display button may be a toggle button.
  • the information processing unit 102 causes the window to be displayed in the processing condition setting screen, and then the matrix display button is further touched by the user. Accordingly, the information processing unit 102 closes the displayed window. While it is expected that the window will be frequently confirmed by the first user, if the window is always displayed, it will be difficult to confirm the plot data in the measurement data display area. Therefore, by making the matrix display button a toggle button as described above, it is possible to easily confirm the plot data and improve the convenience of the window.
  • the matrix display button is preferably arranged at the edge of the processing condition setting screen, particularly at the edge of the second display area. This makes it easier for the user to touch the matrix display button.
  • the matrix display button 206 is arranged in the measurement data display area of the second display area, but the button may be arranged in the operation button area.
  • FIG. 16 shows an example of a window displayed by selecting the gate tree display button.
  • Window 227 shown in the figure shows statistical data of the displayed measurement data group.
  • the size of the window may be smaller than the size of the second display area.
  • the area of the window may be, for example, 60% or less, preferably 50% or less of the area of the second display area.
  • the area of the window may be, for example, 20% or more, preferably 30% or more of the area of the second display area. This makes it possible to adjust the parameters in the correction matrix while checking the measurement data displayed in the second display area.
  • the statistical data includes the name of each gate. Further, the statistical data includes the number of events contained in each gate, the ratio of the number of events contained in each gate to the number of events displayed in a certain plot data, and the events contained in each gate to the total number of events. It may include one, two, or all three of the proportions of the numbers.
  • the name of each gate includes the number of events corresponding to each gate and the ratio of the above two types.
  • the display or non-display of the window may be switched by touching the gate tree display button, that is, the gate tree display button may be a toggle button.
  • the information processing unit 102 causes the window to be displayed in the processing condition setting screen, and then the gate tree display button is further touched by the user. Accordingly, the information processing unit 102 closes the displayed window. While it is assumed that the window is also frequently confirmed by the first user, if the window is always displayed, it becomes difficult to confirm the plot data in the measurement data display area. Therefore, by using the gate tree display button as a toggle button as described above, it is possible to easily confirm the plot data and improve the convenience of the window.
  • the gate tree display button is preferably arranged at the edge of the processing condition setting screen, particularly at the edge of the second display area. This makes it easier for the user to touch the gate tree display button.
  • the gate tree display button 207 is arranged in the measurement data display area of the second display area, but the button may be arranged in the operation button area.
  • the toolbox group displayed by selecting the worksheet toolbox display button, the plot toolbox display button, and the gate toolbox display button can be used. These will be described below.
  • the data input in this way may be included as a part of the operation control data, for example, as a part of "(b) Display control data related to display on the process execution operation screen in the second mode". May be included.
  • event number data data input via area 229 that specifies the number of events to be displayed
  • display format data that specifies the display format of plot data (data input via area 230)
  • Both of these may be included in the display control data of (b) above. It should be noted that these data may be treated as being included in the "(a) processing condition data adopted by the processing apparatus that executes the processing in the second mode".
  • FIG. 18 shows an example of a toolbox displayed by selecting the plot toolbox display button.
  • the toolbox 232 shown in the figure includes buttons for adjusting the settings applied to each plot data or for manipulating each plot data.
  • the toolbox is Area 233 containing one or more buttons for manipulating plot data (including, for example, a new plot button, a plot format change button, a plot data copy button, and a plot data paste button (for overlay analysis)).
  • the axis specifying data (data input via the area 234) that specifies the display format of the axis of the plot data may be included in the display control data of the above (b). It should be noted that these data may be treated as being included in the "(a) processing condition data adopted by the processing apparatus that executes the processing in the second mode".
  • the information processing unit 102 may display the operation panel 260 within, for example, 5 cm, preferably within 4 cm, more preferably within 3 cm, and even more preferably within 2 cm from the touched position.
  • the distance may mean the distance between the touched position and the point closest to the touched position in the area of the operation panel.
  • the operation panel may include one or more operation tool selection buttons.
  • the operation tool selection button may include, for example, one or more tool buttons that are frequently used by the user.
  • the operation tool selection button included in the operation panel may be configured so that the user can change it.
  • the operation tool selection button includes, for example, any one or more buttons included in the plot toolbox and / or any one or more buttons included in the gate toolbox.
  • the operation panel 260 shown in FIG. 32B includes a new plot button, a plot format change button, a plot data copy button, and a plot data paste button among the buttons mentioned with respect to the plot toolbox. Moreover, among the buttons mentioned regarding the gate toolbox, a button for creating a new gate is included.
  • different operation panels may be displayed in the vicinity of the touch position depending on the plot portion to be touched.
  • the information processing unit 102 may display an operation panel (toolbox) for performing X-axis adjustment in the vicinity of the touch position.
  • the information processing unit 102 may display an operation panel (toolbox) for adjusting the Y-axis in the vicinity of the touch position.
  • the information processing unit 102 may display the operation panel (toolbox) for gate adjustment in the vicinity of the touch position in response to the touch in the frame of the gate.
  • the first user touches the axis portion of any of the plot data.
  • the information processing unit 102 has three slider bars 270A, 270B, and three slider bars 270A, 270B, next to the axis of the plot data, as shown in FIG. 33B.
  • Display 270C the slider bar 270A is a slider bar used for adjusting the maximum value of the axis
  • the slider 270B is a slider bar used for adjusting the width of the vicinity of 0 of the axis
  • 270C is a slider bar used to adjust the minimum value of the axis.
  • the information processing unit 102 changes the plot data (display of axis and event data) according to the drag operation of the knob of each slider bar. Even when the drag operation is moved upward or downward beyond the display range of the slider bar, the change of the plot data may be continued. This makes it easy to adjust the axis even when the plot data is displayed small, for example. Although the above three types of slider bars are displayed in FIG. 33B, the information processing unit 102 may display any one or two of these three types. The information processing unit 102 erases the slider when an area other than the slider bar is touched.
  • the information processing unit 102 can display an enlarged image of the touched portion in response to the touch of the data display portion of any of the plots in the second display area.
  • the information processing unit 102 displays an enlarged image of the touched position. Display in the vicinity of the position. The display of the enlarged image will be described below with reference to FIGS. 34A and 34B.
  • each handle may be polygonal (particularly rectangular) or circular, or may be any other shape.
  • the size of each handle (the long side of a rectangle or one side of a square, the diameter of a circle) is, for example, 5 dots to 25 dots, preferably 10 dots to 20 dots in the untouched state, and is touched (the touched state). In the state of being displayed in a large size as described above), it may be, for example, 30 dots to 60 dots, preferably 40 dots to 55 dots. Further, the size of the handle in the touched state may be 1.5 to 5 times, preferably 2 to 4 times the size of the handle in the untouched state. By displaying the touched handle in a large size, the user can easily identify the touched handle.
  • the data input in this way may be included in the operation control data, and in particular, "(c) Instruction data for an operator directed to an operator who operates the processing device in the second mode". May be included as part of.
  • the template specific data including the template name and / or the explanation about the template may be included in the instruction data for the operator in the above (c).
  • the template specific data may further include the number of revisions and / or the creation date of the template.
  • the aliquot setting data includes any one or more data input via the aliquot setting area.
  • the data input in this way may be included as a part of the operation control data, for example, "(a) processing condition data adopted by a processing apparatus that executes the processing in the second mode” or ".
  • (C) It may be included as a part of "instruction data for an operator directed to an operator who operates the processing device in the second mode".
  • the aliquot acquisition instruction data may be included in the instruction data for the operator of (c).
  • the timing setting data may be included in the processing condition data of (a).
  • the order designation field may be configured so that an option indicating that display is necessary can be selected.
  • the first user inputs or selects the adjustment order in the order specification field of each measurement data (plot data) displayed in the second display area, or inputs or selects the necessity of display (particularly no display is required). do.
  • measurement data display setting data is generated. That is, the measurement data display setting data includes data input via the order designation field in this way, and includes, for example, adjustment order data or display necessity data.
  • the generated measurement data display setting data may be included as a part of the operation control data, and in particular, one of the "(b) display control data related to the display on the process execution operation screen in the second mode". May be included as a part.
  • the information processing unit 102 displays a list of selectable templates in the template selection field.
  • the template name may be displayed based on the template property data, and in particular, the template name entered in the template property area in the Template step of the first display mode is displayed. In the figure, "Template A (Granulocyte)" is selected.
  • the information processing unit 102 displays an instruction regarding the gate adjustment of the plot 1 in the instruction column 311 as shown in the figure. ..
  • the bioparticle sorting device 100 may display the instruction based on the operation control data (particularly the instruction data for the operator) input in the first display mode, and in particular, the instruction is input in the memo input field. Display memos (especially instructional memos). The second user can properly execute the gate adjustment by referring to the instruction column.
  • the bioparticle sorting device 100 causes the gate operation button column 312 to be displayed next to the data display column. May be good.
  • the information processing unit 102 can change the size of the gate A according to the dragging. Further, the information processing unit 102 may allow the gate position to be changed based on the operation control data. For example, the information processing unit 102 may change the position of the gate A in response to the second user touching and dragging the gate A. For example, touching and dragging another specific position (for example, an arbitrary position change mark displayed in the gate A or displayed on the line defining the gate A, or the center of the gate A). The information processing unit 102 can move the position of the gate A in the dragging direction in response to dragging (according to) in a state of being touched by the second user.
  • a specific position for example, a size change mark displayed in the gate A or displayed on the line defining the gate A, or a line defining the gate A.
  • the information processing unit 102 may display the confirmation graph data (Reference Plot) to be referred to for the adjustment of the gate C in the data display field 310.
  • the information processing unit 102 can display the confirmation graph data based on the operation control data (particularly, instruction data for the operator, and more particularly reference data).
  • the confirmation graph data includes an image of the plot data acquired in the first display mode and a gate set by the user in the first display mode for the plot data. It's okay to have it. The output of such confirmation graph data to the screen is useful for the user in the second display mode to properly perform the gate adjustment in the plot data.
  • the information processing unit 102 causes the fourth display area to display a screen 313 showing the sorting status, as shown in the figure.
  • the screen displays an area 314 for displaying the number of events and / or the event acquisition speed (eps), and the number and / or the distribution speed (eps). May be good.
  • the information processing unit 102 may display an image 315 (a bar is displayed as the image in the figure) showing the progress of the sorting operation on the screen.
  • An image 316 showing when the aliquot acquisition step is executed may be attached to the bar.
  • the information processing unit 102 may display an image showing the timing based on the control data input in the first display mode, particularly based on the aliquot setting data.
  • the bioparticle sorting device 100 suspends the sorting process and displays, for example, the window 317 shown in FIG. 30. As shown in the figure, the window may display a confirmation method for aliquots and / or current preparative status. In addition, a button for advancing the process is also displayed in the window.
  • the information processing unit 102 displays a screen prompting the second user to select whether to continue the sorting process.
  • the screen includes a continue button for causing the information processing unit 102 to continue the sorting process and a stop button for canceling the sorting process.
  • the information processing unit 102 continues the sorting process in response to the second user selecting the continue button.
  • the bioparticle sorting device 100 cancels the sorting process.
  • the screen may include a readjustment button for readjusting the gate. In response to the second user selecting the readjustment button, the bioparticle sorting device 100 returns the process to the gate adjustment process.
  • the bioparticle sorting device 100 displays a screen showing the sorting result in the fourth display area in the result confirmation step.
  • the number of events and / or the number of fractions may be displayed on the screen.
  • a biological particle sorting device that performs a sorting process on biological particles contained in a biological sample flowing in the flow path (particularly, biological particles flowing in a row in the flow path).
  • the present disclosure may be applied to a biological particle sorting apparatus that performs a sorting process on a group of biological particles existing two-dimensionally or three-dimensionally. That is, the bioparticle sorting apparatus of the present disclosure may be configured to perform a sorting process on a group of bioparticles existing two-dimensionally or three-dimensionally.
  • the biological particle sorting treatment is performed using the particle capturing chip described in JP-A-2020-174598.
  • bioparticle sorting devices to be performed.
  • a biological particle sorting device that performs a sorting process on a group of biological particles existing two-dimensionally on an arbitrary surface
  • a linker capable of decomposing into a certain surface for example, a photodegradable linker
  • From the group of immobilized biological particles (cells), a biological particle sorting device that sorts specific biological particles can be mentioned.
  • These devices acquire a fluorescence signal or a fluorescence image of a bioparticle using an optical detector including, for example, a microscope, and identify the bioparticle to be fractionated based on the acquired fluorescence signal or the fluorescence image. It may be configured as follows. These devices may be configured to extract only the bioparticles thus identified from the well, or release immobilization of only the bioparticles thus identified (eg, immobilize the bioparticles). It may be configured to cleave the linker).
  • the present disclosure discloses a first information processing apparatus that operates in a first display mode that accepts input of operation control data related to bioparticle sorting processing, and a second that operates in a second display mode in which a processing execution operation screen is displayed. Also provides an information processing device and a bioparticle sorting system including.
  • the bioparticle sorting system further includes a bioparticle sorting device operated by the first information processing device or the second information processing device.
  • the bioparticle sorting device is described in 2. above. It may have the configuration described in.
  • the present disclosure also provides the first information processing apparatus included in the bioparticle sorting system.
  • the first information processing apparatus may include, for example, a touch input-capable display unit that displays a processing condition setting screen that accepts input of operation control data related to a preparative process of a biological particle-containing sample.
  • the processing condition setting screen is displayed in 2. above. It may be as described in the above, and the description also applies to the present embodiment.
  • the present disclosure also provides the second information processing apparatus included in the bioparticle sorting system.
  • the second information processing apparatus may include, for example, a display unit capable of touch input for displaying a processing execution operation screen.
  • the operation screen for executing the process is the above 2. It may be as described in the above, and the description also applies to the present embodiment.
  • the information processing device 402a is described in the above 2. Steps S10, S11, and S12 described in (2-1) are executed. Next, the information processing apparatus 402a is described in the above 2.
  • the operation control data is generated by executing the process in the first display mode described in (2-2). More specifically, the information processing apparatus 402a is described in the above 2. It operates as the information processing unit 102 described in (2-2).
  • the information processing device 402a is described in the above 2.
  • the processing condition setting screen described in (2-2) is output to a display unit attached to or connected to the device, and input of the operation control data is received via the screen. Further, in the generation of the operation control data, the sorting process by the biological particle sorting device 401 may be performed.
  • the information processing device 402a transmits the generated operation control data to the bioparticle sorting device 401.
  • the present disclosure may also have the following structure.
  • It is equipped with a touch-input display unit that displays a screen for setting processing conditions that accepts input of operation control data related to the preparative processing of biological particle-containing samples.
  • the processing condition setting screen has a first display area for displaying an operation flow for setting a preparative processing condition for a biological particle-containing sample, and a second display area for displaying measurement data related to the biological particle-containing sample. Including, The first display area is arranged at the end of the processing condition setting screen.
  • Bioparticle sorting device is provided at the end of the processing condition setting screen.
  • the first display area is A procedure button area in which a plurality of processing buttons included in the operation flow are arranged according to the processing order, and A setting information display area that displays the setting information corresponding to the processing button when any processing button is touched, and The bioparticle sorting device according to [1].
  • the first display area is arranged at the left end of the processing condition setting screen, and the procedure button area is arranged at the left end of the first display area, or The first display area is arranged at the right end portion of the processing condition setting screen, and the procedure button area is arranged at the right end portion in the first display area, according to [2].
  • Bioparticle sorting device is A procedure button area in which a plurality of processing buttons included in the operation flow are arranged according to the processing order, and A setting information display area that displays the setting information corresponding to the processing button when any processing button is touched.
  • the second display area is arranged at the right end portion of the processing condition setting screen.
  • the second display area is arranged at the left end of the processing condition setting screen.
  • the bioparticle sorting device according to any one of [1] to [3].
  • the second display area is configured to receive input of gate information for specifying bioparticles to be separated in the process by a touch operation.
  • the bioparticle sorting device according to any one of [1] to [4].
  • the second display area is configured to display one or more plots. When any plot is touched, an operation panel for operating the plot is displayed in the vicinity of the touched position.
  • the bioparticle sorting device according to any one of [1] to [5]. [7] The bioparticle sorting device according to [6], wherein the operation panel includes one or more operation tool selection buttons. [8] The second display area is configured to display one or more plots. The second display area displays one or more operation buttons for displaying data associated with the one or more plots. The bioparticle sorting device according to any one of [1] to [7]. [9] The bioparticle sorting device according to [8], wherein the associated data is back data used to generate the plot. [10] The bioparticle sorting device according to [9], wherein the back data includes statistical information of each gate. [11] The bioparticle sorting device according to [8], wherein the associated data is fluorescence correction matrix data.
  • the bioparticle sorting device according to any one of [9] to [11], wherein the plot can be changed according to the operation of the back data.
  • the second display area is configured to display one or more plots.
  • the bioparticle sorting device which displays a slider bar for changing the display format of any of the plots when the axis is touched.
  • the biological particle sorting device according to [13], wherein the slider bar is a slider bar for adjusting a numerical range or a scale of each axis.
  • the second display area is configured to display one or more plots.
  • the bioparticle sorting device according to any one of [1] to [14], which displays an enlarged image of the touched portion in response to the touch of the data display portion of any of the plots.
  • the second display area is Any one of [1] to [15], including a plot button for manipulating the plots displayed in the area and / or an operation button area including a gate button for manipulating the gates in each plot.
  • the bioparticle sorting device according to. [17] The bioparticle sorting device according to any one of [1] to [16], wherein the display unit is arranged on any surface of the housing of the bioparticle sorting device.
  • the processing condition setting screen has a first display area for displaying an operation flow for setting a preparative processing condition for a biological particle-containing sample, and a second display area for displaying measurement data related to the biological particle-containing sample. Including, The first display area is arranged at the end of the processing condition setting screen. Information processing equipment.
  • Bioparticle sorting device 101
  • Display unit 102

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WO2022080020A1 (ja) 2022-04-21
JPWO2022080022A1 (zh) 2022-04-21
CN116324375A (zh) 2023-06-23
JPWO2022080020A1 (zh) 2022-04-21

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